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1.
PLoS Pathog ; 14(8): e1007273, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-30153307

RESUMEN

Human whipworm (Trichuris trichiura) infects approximately 1 in 15 people worldwide, representing the leading infectious cause of colitis and subsequent, inflammatory bowel disease (IBD). Current control measures focused on mass deworming have had limited success due to low drug efficacies. Vaccination would be an ideal, cost-effective strategy to induce protective immunity, leading to control of infection and transmission. Here we report the identification of whey acidic protein, a whipworm secretory protein, as a strong immunogen for inducing protective efficacy in a surrogate mouse T. muris infection model. The recombinant WAP protein (rTm-WAP49), as well as a single, highly conserved repeat within WAP (fragment 8) expressed as an Na-GST-1 fusion protein (rTm-WAP-F8+Na-GST-1), generate a strong T helper type 2 (Th2) immune response when delivered as subcutaneous vaccines formulated with Montanide ISA 720. Oral challenge with T. muris infective eggs following vaccination led to a significant reduction in worm burden of 48% by rTm-WAP49 and 33% by rTm-WAP-F8+Na-GST-1. The cellular immune correlates of protection included significant antigen-specific production of Th2 cytokines IL-4, IL-9, and IL-13 by cells isolated from the vaccine-draining inguinal lymph nodes, parasite-draining mesenteric lymph nodes, and spleen in mice vaccinated with either rTm-WAP49 or rTm-WAP-F8+Na-GST-1. The humoral immune correlates included a high antigen-specific ratio of IgG1 to IgG2a, without eliciting an IgE-mediated allergic response. Immunofluorescent staining of adult T. muris with WAP antisera identified the worm's pathogenic stichosome organ as the site of secretion of native Tm-WAP protein into the colonic mucosa. Given the high sequence conservation for the WAP proteins from T. muris and T. trichiura, the results presented here support the WAP protein to be further evaluated as a potential human whipworm vaccine candidate.


Asunto(s)
Inmunidad , Proteínas de la Leche/inmunología , Tricuriasis/prevención & control , Trichuris/inmunología , Animales , Anticuerpos Antihelmínticos/metabolismo , Antígenos Helmínticos/genética , Antígenos Helmínticos/inmunología , Antígenos Helmínticos/farmacología , Inmunidad/efectos de los fármacos , Inmunidad/genética , Masculino , Ratones , Ratones Endogámicos AKR , Ratones Noqueados , Ratones SCID , Proteínas de la Leche/genética , Proteínas de la Leche/farmacología , Tricuriasis/inmunología , Trichuris/genética , Vacunación/métodos
2.
Asian Pac J Cancer Prev ; 16(13): 5349-57, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26225677

RESUMEN

BACKGROUND: Breast cancer is the most common cancer and the leading cause of cancer mortality among women of all ethnic and age groups in Malaysia. Delay in seeking help for breast cancer symptoms is preventable and by identifying possible factors for delayed diagnosis, patient prognosis and survival rates could be improved. OBJECTIVES: This narrative review aimed to understand and evaluate the level of in-depth breast cancer knowledge in terms of clinical breast examination and breast self-examination, and other important aspects such as side-effects and risk factors in Malaysian females. Since Malaysia is multicultural, this review assessed social perceptions, cultural beliefs and help-seeking behaviour in respect to breast cancer among different ethnic groups, since these may impinge on efforts to 'avoid' the disease. MATERIALS AND METHODS: A comprehensive literature search of seven databases was performed from December 2015 to January 2015. Screening of relevant published journals was also undertaken to identify available information related to the knowledge, perception and help-seeking behaviour of Malaysian women in relation to breast cancer. RESULTS: A total of 42 articles were appraised and included in this review. Generally, women in Malaysia had good awareness of breast cancer and its screening tools, particularly breast self-examination, but only superficial in-depth knowledge about the disease. Women in rural areas had lower levels of knowledge than those in urban areas. It was also shown that books, magazines, brochures and television were among the most common sources of breast cancer information. Delay in presentation was attributed mainly to a negative social perception of the disease, poverty, cultural and religion practices, and a strong influence of complementary and alternative medicine, rather than a lack of knowledge. CONCLUSIONS: This review highlighted the need for an intensive and in-depth breast cancer education campaigns using media and community health programmes, even with the existing good awareness of breast cancer. This is essential in order to avoid misconceptions and to frame the correct mind-set about breast cancer among women in Malaysia. Socio-cultural differences and religious practices should be taken into account by health care professionals when advising on breast cancer. Women need to be aware of the risk factors and symptoms of breast cancer so that early diagnosis can take place and the chances of survival improved.


Asunto(s)
Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/terapia , Autoexamen de Mamas/psicología , Diagnóstico Tardío , Conductas Relacionadas con la Salud , Conocimientos, Actitudes y Práctica en Salud , Neoplasias de la Mama/psicología , Femenino , Humanos , Malasia , Aceptación de la Atención de Salud , Percepción , Pronóstico , Factores de Riesgo
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